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Exosomes derived from retinoblastoma cells enhance tumour deterioration by infiltrating the microenvironment.

ABSTRACT: The survival of young children (under 5 years of age) with malignant retinoblastoma remains poor, and clarification of the mechanism underlying tumour development is urgently needed. The present study aimed to reveal the role of exosomes (EXOs) from retinoblastoma cells in tumour development. The in vitro data indicated that EXOs derived from WERI?Rb1 cells significantly inhibited the antitumour activity of macrophages and induced bone marrow mesenchymal stem cells to promote tumour growth via an increase in monocyte chemotactic protein 1 (also known as C?C motif chemokine ligand 2) levels. In vivo data from a xenotransplantation model also showed that EXOs infiltrated the spleen, which induced a decrease in leukocytes and natural killer (NK) cells. Accordingly, the proportion of tumour?associated macrophages was increased and the proportion of NK cells was decreased in tumours injected with EXOs compared with those injected with the control. EXOs were absorbed by Kupffer cells, and more metastases were observed in the liver. Thus, these results suggested that EXOs derived from retinoblastoma promoted tumour progression by infiltrating the microenvironment. Moreover, microRNAs (miRs), including miR?92a, miR?20a, miR?129a and miR?17, and C?X?C chemokine receptor type 4 and thrombospondin?1 were detectable in EXOs, which might account for EXO?mediated tumour deterioration.

SUBMITTER: Chen S

PROVIDER: S-EPMC7716702 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Exosomes derived from retinoblastoma cells enhance tumour deterioration by infiltrating the microenvironment.

Chen Shuilian S Chen Xi X Qiu Jin J Chen Pei P Han Xiaokun X Wu Yihui Y Zhuang Jiejie J Yang Meng M Wu Chuangran C Wu Nandan N Yang Ying Y Ge Jian J Yu Keming K Zhuang Jing J

Oncology reports 20201118 1

The survival of young children (under 5 years of age) with malignant retinoblastoma remains poor, and clarification of the mechanism underlying tumour development is urgently needed. The present study aimed to reveal the role of exosomes (EXOs) from retinoblastoma cells in tumour development. The in vitro data indicated that EXOs derived from WERI‑Rb1 cells significantly inhibited the antitumour activity of macrophages and induced bone marrow mesenchymal stem cells to promote tumour growth via a ...[more]

PMID: 33416154

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Project description:BACKGROUND:We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC?+?radiotherapy (RT). METHODS:We have measured tumor growth and metastasis formation, of subcutaneous human melanoma A375 xenografts on NOD/SCID-gamma mice, and the response of tumors to treatment with radiotherapy (2 Gy), mesenchymal cells (MSC), mesenchymal cells plus radiotherapy, and without any treatment. Using proteomic analysis, we studied the cargo of the exosomes released by the MSC treated with 2 Gy, compared with the cargo of exosomes released by MSC without treatment. RESULTS:The tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5% in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover, the number of metastatic foci found in the internal organs of the mice treated with MSC?+?RT was 60% less than the mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor growth delay and metastasis control after treatment. CONCLUSIONS:Our results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the control of tumor growth and metastasis.

Dataset Information

Exosomes derived from retinoblastoma cells enhance tumour deterioration by infiltrating the microenvironment.

Publications

Exosomes derived from retinoblastoma cells enhance tumour deterioration by infiltrating the microenvironment.

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